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1.
Prev Med ; : 106860, 2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-34687733

RESUMEN

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.

3.
BMJ Nutr Prev Health ; 4(1): 257-266, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34308134

RESUMEN

Background: Several studies have hypothesised that dietary habits may play an important role in COVID-19 infection, severity of symptoms, and duration of illness. However, no previous studies have investigated the association between dietary patterns and COVID-19. Methods: Healthcare workers (HCWs) from six countries (France, Germany, Italy, Spain, UK, USA) with substantial exposure to COVID-19 patients completed a web-based survey from 17 July to 25 September 2020. Participants provided information on demographic characteristics, dietary information, and COVID-19 outcomes. We used multivariable logistic regression models to evaluate the association between self-reported diets and COVID-19 infection, severity, and duration. Results: There were 568 COVID-19 cases and 2316 controls. Among the 568 cases, 138 individuals had moderate-to-severe COVID-19 severity whereas 430 individuals had very mild to mild COVID-19 severity. After adjusting for important confounders, participants who reported following 'plant-based diets' and 'plant-based diets or pescatarian diets' had 73% (OR 0.27, 95% CI 0.10 to 0.81) and 59% (OR 0.41, 95% CI 0.17 to 0.99) lower odds of moderate-to-severe COVID-19 severity, respectively, compared with participants who did not follow these diets. Compared with participants who reported following 'plant-based diets', those who reported following 'low carbohydrate, high protein diets' had greater odds of moderate-to-severe COVID-19 (OR 3.86, 95% CI 1.13 to 13.24). No association was observed between self-reported diets and COVID-19 infection or duration. Conclusion: In six countries, plant-based diets or pescatarian diets were associated with lower odds of moderate-to-severe COVID-19. These dietary patterns may be considered for protection against severe COVID-19.

4.
Can J Ophthalmol ; 2021 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-34303640

RESUMEN

OBJECTIVE: To compare the accuracy of intraoperative wavefront aberrometry to preoperative biometry formulae for predicting intraocular lens power. DESIGN: Retrospective, consecutive case series. PARTICIPANTS: Eyes undergoing cataract extraction with at least 1 month of follow-up after surgery at an ambulatory surgical centre in Toronto. METHODS: Consecutive sample of 228 cataract extractions with monofocal, trifocal, or toric intraocular lens implantation from November 1, 2017, to December 31, 2019. The spherical equivalent was predicted preoperatively with Barrett Universal II, Hill-Radial Basis Function (RBF), SRK/T, Holladay I, Holladay II, Haigis, and HofferQ using biometry measurements and intraoperatively with wavefront aberrometry. The primary outcomes were mean prediction error and proportion of eyes with a spherical equivalent within 0.5 D of the refractive target at postoperative month 1. RESULTS: The analysis included 159 eyes with 52% females and a mean age of 69.4 years. Formulae with the lowest mean prediction error were Hill-RBF (0.32 D ± 0.02 D), Barrett Universal II (0.32 D ± 0.02 D), intraoperative aberrometry (0.32 D ± 0.02 D), SRK/T (0.33 D ± 0.02 D), Holladay II (0.34 D ± 0.03 D), Holladay I (0.35 D ± 0.02 D), Haigis (0.37 D ± 0.02 D), and HofferQ (0.42 D ± 0.02 D). There were no statistically significant differences between intraoperative aberrometry and the preoperative formulae. Formulae with the highest proportion of eyes within 0.5 D of the refractive target were intraoperative aberrometry (82%), Barrett Universal II (81%), Hill-RBF (80%), SRK/T (77%), Holladay II (76%), Holladay I (75%), Haigis (71%), and HofferQ (70%). CONCLUSIONS: Intraoperative aberrometry and modern preoperative biometry formulae are equally effective at reaching the refractive target. In normal eyes, intraoperative aberrometry does not appear to provide any additional benefit to modern prediction formulae.

5.
Int Ophthalmol ; 2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34318369

RESUMEN

PURPOSE: To evaluate the accuracy of 12 intraocular lens (IOL) power calculations: Barrett Universal II, EVO, Haigis, Hill-RBF version 2.0, Hoffer Q, Holladay 1, Holladay 2, Kane, Olsen, SRK/T, Super Formula and T2. METHODS: In this retrospective consecutive case series, cataract extraction and IOL implantation cases in Toronto, Canada, were recruited between 2017 and 2019. Refractive predictions were compared to the observed 1-month postoperative spherical equivalent to determine the refractive error for each formula cohort. Subgroup analysis stratified eyes into short (≤ 22.5 mm)-, intermediate (22.5 mm-25.5 mm)- and long (≥ 25.5 mm)-axial length (AL) cohorts. The primary outcome was the percentage of cases within ± 0.50D of refractive error. RESULTS: Overall, 764 cataract cases were analyzed. Formulas with the highest percentage of eyes within ± 0.50D of refractive error, in decreasing order, were: Kane (77.7%), Barrett Universal II (77.4%), EVO (76.6%), T2 (76.4%), Super (75.9%), Holladay 1 (75.4%), Hill-RBF 2.0 (74.7%), SRK/T (72.6%), Hoffer Q (72.5%), Haigis (71.7%), Olsen (67.4%) and Holladay 2 (67.3%). For short-AL eyes, the Holladay 1 formula was most accurate (n = 69, 78.3% within ± 0.50D), and for long-AL eyes, the Barrett Universal II formula was most accurate (n = 116, 76.7% within ± 0.50D). Kane, Barrett, EVO, T2 and Super formulas led to a significantly lower mean absolute error compared to the open-source calculations with optimized lens constants (p-value: < 0.001-0.042). CONCLUSIONS: The Kane formula was the most accurate formula for the overall analysis. The Holladay 1 calculation was most accurate for short-AL cases, whereas the Barrett Universal II was superior for long-AL eyes.

8.
J Biomol NMR ; 75(2-3): 83-87, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33538948

RESUMEN

A simple and cost-effective protocol is presented for expression of perdeuterated, Ile/Leu/Val 1H/13C methyl protonated proteins from 100 ml cultures in M9 ++ /D2O medium induced at high (OD600 ~ 10) cell density in shaker flasks. This protocol, which is an extension of our previous protocols for expression of 2H/15N/13C and 1H/13C labeled proteins, yields comparable quantities of protein from 100 ml cell culture to those obtained using a conventional 1 L culture with M9/D2O medium, while using three-fold less α-ketoisovaleric (1,2,3,4-13C4; 3,4',4',4'-d4) and α-ketobutyric (13C4; 3,3-d2) acid precursors.

10.
PLoS Comput Biol ; 17(2): e1008720, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33630864

RESUMEN

Increased availability of drug response and genomics data for many tumor cell lines has accelerated the development of pan-cancer prediction models of drug response. However, it is unclear how much between-tissue differences in drug response and molecular characteristics may contribute to pan-cancer predictions. Also unknown is whether the performance of pan-cancer models could vary by cancer type. Here, we built a series of pan-cancer models using two datasets containing 346 and 504 cell lines, each with MEK inhibitor (MEKi) response and mRNA expression, point mutation, and copy number variation data, and found that, while the tissue-level drug responses are accurately predicted (between-tissue ρ = 0.88-0.98), only 5 of 10 cancer types showed successful within-tissue prediction performance (within-tissue ρ = 0.11-0.64). Between-tissue differences make substantial contributions to the performance of pan-cancer MEKi response predictions, as exclusion of between-tissue signals leads to a decrease in Spearman's ρ from a range of 0.43-0.62 to 0.30-0.51. In practice, joint analysis of multiple cancer types usually has a larger sample size, hence greater power, than for one cancer type; and we observe that higher accuracy of pan-cancer prediction of MEKi response is almost entirely due to the sample size advantage. Success of pan-cancer prediction reveals how drug response in different cancers may invoke shared regulatory mechanisms despite tissue-specific routes of oncogenesis, yet predictions in different cancer types require flexible incorporation of between-cancer and within-cancer signals. As most datasets in genome sciences contain multiple levels of heterogeneity, careful parsing of group characteristics and within-group, individual variation is essential when making robust inference.


Asunto(s)
Antineoplásicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias/tratamiento farmacológico , Algoritmos , Área Bajo la Curva , Línea Celular Tumoral , Variaciones en el Número de Copia de ADN , Inhibidores Enzimáticos/farmacología , Dosificación de Gen , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Genómica , Humanos , MAP Quinasa Quinasa 1/antagonistas & inhibidores , Aprendizaje Automático , Mutación Puntual , Polimorfismo de Nucleótido Simple , ARN/genética , ARN/metabolismo , ARN Mensajero/metabolismo , Análisis de Regresión
11.
Int Ophthalmol ; 41(4): 1521-1530, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33511513

RESUMEN

PURPOSE: To evaluate differences in preoperative measurements and refractive outcomes between ultrasound and optical biometry when using the Barrett Universal II intraocular lens (IOL) power formula. METHODS: In this consecutive case series, cataract extraction and IOL implantation cases from two surgical centers in Toronto, Canada, were recruited between January 2015 and July 2017. Differences between ultrasound (applanation or immersion A-scan) and optical biometry (IOLMaster 500) were compared for axial length (AL), anterior chamber depth and refractive outcomes. The primary outcome was the percentage of cases in each cohort within ± 0.50D of refractive error. RESULTS: In total, 527 cataract cases underwent IOLMaster testing. Of these, 329 eyes (62.4%) were also measured by applanation A-scan, and the other 198 eyes (37.6%) received immersion A-scan testing. Applanation ultrasound led to 5.8%, 16.0% and 46.4% of eyes within ± 0.25D, ± 0.50D and ± 1.00D of refractive error, respectively, whereas the IOLMaster 500 led to 48.5%, 77.1% and 94.9%, respectively (n = 293, ± 0.50D: p < 0.001). Immersion ultrasound led to 31.2%, 57.6% and 91.2% of eyes within ± 0.25D, ± 0.50D and ± 1.00D of refractive error, respectively, whereas the IOLMaster 500 led to 42.4%, 72.0% and 92.0%, respectively (n = 125, ± 0.50D: p = 0.001). Applanation (n = 329, A-scan AL: 23.64 ± 1.67 mm, IOLMaster AL: 24.20 ± 1.70 mm, p < 0.001) and immersion ultrasound (n = 198, A-scan AL: 25.01 ± 2.06 mm, IOLMaster AL: 25.08 ± 2.13 mm, p = 0.002) yielded significantly lower AL values compared to optical biometry measurements. CONCLUSIONS: Optical biometry yielded a significantly larger percentage of cases within ± 0.50D of refractive error compared to ultrasound biometry when using the Barrett Universal II IOL power formula.


Asunto(s)
Extracción de Catarata , Catarata , Lentes Intraoculares , Biometría , Canadá , Catarata/diagnóstico , Humanos , Refracción Ocular
12.
IEEE Trans Biomed Eng ; 68(2): 628-638, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32746062

RESUMEN

OBJECTIVE: Musculoskeletal models play an important role in surgical planning and clinical assessment of gait and movement. Faster and more accurate simulation of muscle paths in such models can result in better predictions of forces and facilitate real-time clinical applications, such as rehabilitation with real-time feedback. We propose a novel and efficient method for computing wrapping paths across arbitrary surfaces, such as those defined by bone geometry. METHODS: A muscle path is modeled as a massless, frictionless elastic strand that uses artificial forces, applied independently of the dynamic simulation, to wrap tightly around intervening obstacles. Contact with arbitrary surfaces is computed quickly using a distance grid, which is interpolated quadratically to provide smoother results. RESULTS: Evaluation of the method demonstrates good accuracy, with mean relative errors of 0.002 or better when compared against simple cases with exact solutions. The method is also fast, with strand update times of around 0.5 msec for a variety of bone shaped obstacles. CONCLUSION: Our method has been implemented in the open source simulation system ArtiSynth (www.artisynth.org) and helps solve the problem of muscle wrapping around bones and other structures. SIGNIFICANCE: Muscle wrapping on arbitrary surfaces opens up new possibilities for patient-specific musculoskeletal models where muscle paths can directly conform to shapes extracted from medical image data.


Asunto(s)
Modelos Biológicos , Músculo Esquelético , Huesos , Simulación por Computador , Humanos
13.
Bone Jt Open ; 1(6): 302-308, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33215118

RESUMEN

Aims: Elective operating was halted during the COVID-19 pandemic to increase the capacity to provide care to an unprecedented volume of critically unwell patients. During the pandemic, the orthopaedic department at the Aneurin Bevan University Health Board restructured the trauma service, relocating semi-urgent ambulatory trauma operating to the isolated clean elective centre (St. Woolos' Hospital) from the main hospital receiving COVID-19 patients (Royal Gwent Hospital). This study presents our experience of providing semi-urgent trauma care in a COVID-19-free surgical unit as a safe way to treat trauma patients during the pandemic and a potential model for restarting an elective orthopaedic service. Methods: All patients undergoing surgery during the COVID-19 pandemic at the orthopaedic surgical unit (OSU) in St. Woolos' Hospital from 23 March 2020 to 24 April 2020 were included. All patients that were operated on had a telephone follow-up two weeks after surgery to assess if they had experienced COVID-19 symptoms or had been tested for COVID-19. The nature of admission, operative details, and patient demographics were obtained from the health board's electronic record. Staff were assessed for sickness, self-isolation, and COVID-19 status. Results: A total of 58 surgical procedures were undertaken at the OSU during the study period; 93% (n = 54) of patients completed the telephone follow-up. Open reduction and internal fixation of ankle and wrist fractures were the most common procedures. None of the patients nor members of their households had developed symptoms suggestive of COVID-19 or required testing. No staff members reported sick days or were advised by occupational health to undergo viral testing. Conclusion: This study provides optimism that orthopaedic patients planned for surgery can be protected from COVID-19 nosocomial transmission at separate COVID-19-free sites.Cite this article: Bone Joint Open 2020;1-6:302-308.

15.
Cell Chem Biol ; 27(7): 780-792.e5, 2020 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-32386595

RESUMEN

Chlorcyclizine (CCZ) is a potent hepatitis C virus (HCV) entry inhibitor, but its molecular mechanism is unknown. Here, we show that CCZ directly targets the fusion peptide of HCV E1 and interferes with the fusion process. Generation of CCZ resistance-associated substitutions of HCV in vitro revealed six missense mutations in the HCV E1 protein, five being in the putative fusion peptide. A viral fusion assay demonstrated that CCZ blocked HCV entry at the membrane fusion step and that the mutant viruses acquired resistance to CCZ's action in blocking membrane fusion. UV cross-linking of photoactivatable CCZ-diazirine-biotin in both HCV-infected cells and recombinant HCV E1/E2 protein demonstrated direct binding to HCV E1 glycoprotein. Mass spectrometry analysis revealed that CCZ cross-linked to an E1 sequence adjacent to the putative fusion peptide. Docking simulations demonstrate a putative binding model, wherein CCZ binds to a hydrophobic pocket of HCV E1 and forms extensive interactions with the fusion peptide.

16.
BMJ ; 369: m1412, 2020 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-32291268
17.
BMC Genomics ; 21(1): 159, 2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-32054475

RESUMEN

BACKGROUND: Gene expression is regulated by DNA-binding transcription factors (TFs). Together with their target genes, these factors and their interactions collectively form a gene regulatory network (GRN), which is responsible for producing patterns of transcription, including cyclical processes such as genome replication and cell division. However, identifying how this network regulates the timing of these patterns, including important interactions and regulatory motifs, remains a challenging task. RESULTS: We employed four in vivo and in vitro regulatory data sets to investigate the regulatory basis of expression timing and phase-specific patterns cell-cycle expression in Saccharomyces cerevisiae. Specifically, we considered interactions based on direct binding between TF and target gene, indirect effects of TF deletion on gene expression, and computational inference. We found that the source of regulatory information significantly impacts the accuracy and completeness of recovering known cell-cycle expressed genes. The best approach involved combining TF-target and TF-TF interactions features from multiple datasets in a single model. In addition, TFs important to multiple phases of cell-cycle expression also have the greatest impact on individual phases. Important TFs regulating a cell-cycle phase also tend to form modules in the GRN, including two sub-modules composed entirely of unannotated cell-cycle regulators (STE12-TEC1 and RAP1-HAP1-MSN4). CONCLUSION: Our findings illustrate the importance of integrating both multiple omics data and regulatory motifs in order to understand the significance regulatory interactions involved in timing gene expression. This integrated approached allowed us to recover both known cell-cycles interactions and the overall pattern of phase-specific expression across the cell-cycle better than any single data set. Likewise, by looking at regulatory motifs in the form of TF-TF interactions, we identified sets of TFs whose co-regulation of target genes was important for cell-cycle expression, even when regulation by individual TFs was not. Overall, this demonstrates the power of integrating multiple data sets and models of interaction in order to understand the regulatory basis of established biological processes and their associated gene regulatory networks.


Asunto(s)
Regulación Fúngica de la Expresión Génica , Redes Reguladoras de Genes , Genes cdc , Genómica , Saccharomyces cerevisiae/genética , Biología Computacional/métodos , Genómica/métodos , Aprendizaje Automático , Unión Proteica , Mapeo de Interacción de Proteínas , Mapas de Interacción de Proteínas , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Factores de Transcripción/metabolismo
18.
J Med Chem ; 63(4): 1660-1670, 2020 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-31990537

RESUMEN

Endothelial lipase (EL) hydrolyzes phospholipids in high-density lipoprotein (HDL) resulting in reduction in plasma HDL levels. Studies with murine transgenic, KO, or loss-of-function variants strongly suggest that inhibition of EL will lead to sustained plasma high-density lipoprotein cholesterol (HDL-C) increase and, potentially, a reduced cardiovascular disease (CVD) risk. Herein, we describe the discovery of a series of oxadiazole ketones, which upon optimization, led to the identification of compound 12. Compound 12 was evaluated in a mouse pharmacodynamics (PD) model and demonstrated a 56% increase in plasma HDL-C. In a mouse reverse cholesterol transport study, compound 12 stimulated cholesterol efflux by 53% demonstrating HDL-C functionality.


Asunto(s)
HDL-Colesterol/metabolismo , Inhibidores Enzimáticos/farmacología , Cetonas/farmacología , Lipasa/antagonistas & inhibidores , Oxadiazoles/farmacología , Animales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacocinética , Cetonas/síntesis química , Cetonas/farmacocinética , Masculino , Ratones Endogámicos C57BL , Estructura Molecular , Oxadiazoles/síntesis química , Oxadiazoles/farmacocinética , Relación Estructura-Actividad
19.
Ecotoxicology ; 29(8): 1174-1182, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31520201

RESUMEN

We investigated mercury (Hg) blood concentrations in Bicknell's thrush (Catharus bicknelli) and Swainson's thrush (C. ustulatus), congeneric long-distance migratory songbirds, from 2000-2017 at a montane forest site in north-central Vermont. We analyzed variation in blood Hg of both species using mixed-effects models, incorporating atmospheric wet Hg deposition data from a nearby sampling location. Although Hg deposition varied among years and seasonally, we detected no temporal trend in either atmospheric deposition or blood Hg, nor evidence of a relationship between the two. Sampling date had the strongest effect on blood Hg concentration, which declined seasonally, followed by age and sex of the individual. The data did not support an effect of species. We believe that the absence of a clear relationship between local atmospheric deposition and thrush blood Hg concentrations suggests that Hg cycling dynamics, mechanisms of transfer, and timing of uptake by montane forest biota are complex and poorly understood. The blood Hg concentrations of ~0.07-0.1 µg/g we documented in Bicknell's and Swainson's thrush are below those found to negatively impact physiological or reproductive endpoints in other invertivorous terrestrial passerines. To better evaluate the validity of Bicknell's thrush as a bioindicator of MeHg availability in montane forest ecosystems, we recommend (1) effects-based investigations, (2) a more robust understanding of Hg and MeHg cycling, (3) more clear geospatial and temporal links between Hg deposition and biotic uptake, and (4) more thorough documentation of Hg burdens across the species' annual cycle.


Asunto(s)
Monitoreo del Ambiente , Contaminantes Ambientales/sangre , Mercurio/sangre , Passeriformes/sangre , Migración Animal , Animales , Aves , Vermont
20.
Breast Cancer Res Treat ; 179(2): 337-347, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31655920

RESUMEN

PURPOSE: There is a need for biomarkers of drug efficacy for targeted therapies in triple-negative breast cancer (TNBC). As a step toward this, we identify multi-omic molecular determinants of anti-TNBC efficacy in cell lines for a panel of oncology drugs. METHODS: Using 23 TNBC cell lines, drug sensitivity scores (DSS3) were determined using a panel of investigational drugs and drugs approved for other indications. Molecular readouts were generated for each cell line using RNA sequencing, RNA targeted panels, DNA sequencing, and functional proteomics. DSS3 values were correlated with molecular readouts using a FDR-corrected significance cutoff of p* < 0.05 and yielded molecular determinant panels that predict anti-TNBC efficacy. RESULTS: Six molecular determinant panels were obtained from 12 drugs we prioritized based on their efficacy. Determinant panels were largely devoid of DNA mutations of the targeted pathway. Molecular determinants were obtained by correlating DSS3 with molecular readouts. We found that co-inhibiting molecular correlate pathways leads to robust synergy across many cell lines. CONCLUSIONS: These findings demonstrate an integrated method to identify biomarkers of drug efficacy in TNBC where DNA predictions correlate poorly with drug response. Our work outlines a framework for the identification of novel molecular determinants and optimal companion drugs for combination therapy based on these correlates.


Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/etiología , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Biología Computacional/métodos , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos/genética , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Perfilación de la Expresión Génica , Humanos , Mutación , Proteómica , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/metabolismo
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